This invention relates generally to the field of charged particle trapping and, in particular, to the use of a charged particle trap for time-of-flight mass spectrometry.
Time-of-flight mass spectrometry (TOF-MS) is a process by which charged particles, such as ions, can be separated according to their mass. Assuming all the charged particles have the same energy, they will traverse a fixed distance in different amounts of time depending on their mass. Particles having a larger mass will take more time to travel across the fixed distance, resulting in a spectrum of flight times, from which the masses of the individual charged particles can be determined by a detector. The main advantages of TOF-MS techniques lie in fast acquisition time, high throughput, and virtually unlimited mass range, the latter of which is particularly important for methods of the production of ions of large biological molecules in the gas phase.
It is known that the resolution of TOF-MS instruments can be improved by increasing the length of the flight paths of charged particles before the charged particles are steered into a detector. This is known to be achieved by the multiple folding of the flight path by using electrode mirrors.
U.S. Pat. No. 5,880,466 (U.S. ""466) to Benner discloses the trapping of a single, highly charged DNA molecule in an evacuated charged-particle trap, between the trap""s two parallel sets of electrode mirrors with applied voltages that establish an electrostatic situation analogous to an optical resonator. The electrode mirrors cycle the charged molecule back and forth many times through a detector tube mounted between the two mirrors. An induced image charge signal whose amplitude is proportional to the molecule""s net charge is read by the detector on the molecule""s every pass through the detector tube, based on which the molecule""s charge, flight time and, consequently, its mass, are determined. It is inherent to any known ion-producing source that successive particles introduced into the trap have an unavoidable range of initial energies, and therefore different flight times even if their masses are equal. Therefore, in order to obtain high resolution of measurement in the charged-particle trap of U.S. ""466, the trapping procedure must be repeated a large number of times for which an average time of flight for all the molecules can be statistically attained. Also, in order to produce a signal that can be distinguished by the detector from baseline noise, the single trapped particle must carry a relatively large number of charges. To create a particle having such a large net charge, U.S. ""466 makes use of an electrospray ionization (ESI) source.
The present invention provides for a novel method of simultaneously trapping a plurality of charged particles in a charged particle trap consisting of first and second electrode mirrors having a common optical axis. These mirrors are arranged in alignment at the two extremities of the trap and are capable, when voltage is applied thereto, of creating respective electric fields defined by key field parameters and configured to reflect the charged particles and to keep at least part of them oscillating between the mirrors. The method by which this is performed includes introducing into the trap, along the optical axis, a beam of charged particles having pre-determined key beam parameters, and establishing such field parameters, for at least one of the mirrors, as to cause bunching among charged particles in the beam.
By the xe2x80x98key beam parametersxe2x80x99, it is meant the main properties of the beam, such as the number of charged particles in the beam, charge on the particles in the beam, length, density, radius, and volume of the beam, energy and velocities of the particles in the beam. For the purposes of the present description, the length of the trap is also considered a key beam parameter since the oscillation frequency of the beam is dependent thereof. By the xe2x80x98key field parametersxe2x80x99, it is meant such main properties of the electric fields created by the mirrors as the number of electrodes in each electrode mirror, the geometrical arrangement of the electrodes, and the voltage applied to the electrodes.
By xe2x80x98bunchingxe2x80x99, it is meant a synchronization effect, believed to have been discovered by the authors of the present invention, in which oscillating ions having like charges and slightly different velocities when reflected by an electric field of a certain configuration, surprisingly move together, despite the Coulombie repulsion force acting between the ions, the slightly different velocities of the ions and the various path lengths over which the ions can be stored.
The method of the present invention is particularly useful when applied in TOF-MS, because it enables the detection and measurement of a plurality of charged particles, in spite of the particles"" having a range of energies unavoidably created by an ion-producing source. Thereby, the necessity is avoided of repeating the trapping procedure for one particle after another, as in U.S. Pat. No. 5,880,466.
If a bunch of charged particles were introduced into the trap in the manner described in the prior art reference, the bunch would quickly expand until its time of flight could no longer be detected. The method of achieving the bunching phenomenon of the present invention prevents a bunch of charged particles oscillating within the trap from its natural expansion and allows for the prolonged oscillating flight time of the bunch necessary for high resolution in TOF-MS. Therefore, the trapping time of a plurality of charged particles becomes limited only by the extent of evacuation in the trap. Bunching not only facilitates the spectrometry process by allowing a plurality of particles to be simultaneously measured, thereby requiring less time and effort to perform the process, it also allows for each charged particle in the bunch to carry but a single or double charge, because collectively, the particles have a net charge large enough to produce a discernible signal. The latter aspect is of particular importance because it enables the trap to detect all kinds of particles of equal charges, regardless of their mass and charge. Thus, ion sources producing bunches of singly or doubly charged particles, such as matrix-assisted laser desorption/ionization (MALDI), may be used. MALDI is more popular and much more prevalent than the ESI technique used in U.S. Pat. No. 5,880,466.